1.Administration of Psoralea corylifolia L. (Buguzhi) during pregnancy causes mild liver injury in mouse mothers and weaned offspring
Chenyue LIU ; Jingzhuo TIAN ; Yan YI ; Chunying LI ; Yong ZHAO ; Jiayin HAN ; Lianmei WANG ; Suyan LIU ; Yushi ZHANG ; Chen PAN ; Shasha QIN ; Jing MENG ; Sulakkana NOIPRASERT ; Aihua LIANG
Science of Traditional Chinese Medicine 2025;3(2):168-177
Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.
2.Toxicological evaluation of aristolochic acid II following single and repeated oral administration over a 24-week period
Yan YI ; Chunying LI ; Yong ZHAO ; Jingzhuo TIAN ; Yuan WANG ; Yushi ZHANG ; Suyan LIU ; Chen PAN ; Lianmei WANG ; Shuangrong GAO ; Jianyin HAN ; Zhong XIAN ; Chenyue LIU ; Dunfang WANG ; Jing MENG ; Meiting LIU ; Aihua LIANG
Science of Traditional Chinese Medicine 2025;3(4):366-377
Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.
3.Qualitative Analysis of Metabolites of Aristolochiae Fructus Aqueous Extract in Rats
Fang WANG ; Chunying LI ; Yan YI ; Suyan LIU ; Yong ZHAO ; Jing MENG ; Jingzhuo TIAN ; Lianmei WANG ; Jiayin HAN ; Chen PAN ; Yushi ZHANG ; Chenyue LIU ; Shasha QIN ; Dunfang WANG ; Zhong XIAN ; Xuan TANG ; Meiting LIU ; Aihua LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):112-121
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MSE) technique, we identified qualitatively the metabolites of aristolochic acid(AAs) in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus(AFE) and Aristolochic acid Ⅰ(AAⅠ). MethodSD rats were selected and administered AFE(110 g·kg-1·d-1) or AAⅠ(5 mg·kg-1·d-1) by oral for 5 days, respectively. Serum, urine and feces were collected after administration. Through sample pretreatment, ACQUITY UPLC BEH C18 column(2.1 mm×100 mm, 1.7 μm) was used with the mobile phase of 0.01% formic acid methanol(A)-0.01% formic acid water(B, containing 5 mmol·L-1 ammonium acetate) for gradient elution(0-1 min, 10%B; 1-7 min, 10%-75%B; 7-7.2 min, 75%-95%B; 7.2-10.2 min, 95%B; 10.2-10.3 min, 95%-10%B; 10.3-12 min, 10%B) at a flow rate of 0.3 mL·min-1. Positive ion mode of electrospray ionization(ESI+) was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system, the Pathway-MSE was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples(serum, urine and feces), and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group, 6, 10, 13 common metabolites and 14, 20, 30 unique metabolites were identified in biological samples(serum, urine and feces) of AFE group, respectively. Moreover, the main AAs components always followed the metabolic processes of demethylation, nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group, prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ[AAⅠa, aristolochic lactam Ⅰ(ALⅠ)a, 7-OHALⅠ and its conjugated derivatives] in biological samples were significantly increased in AFE group(P<0.05, P<0.01), except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group(P<0.01). In addition, a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo, the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ, and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.
4.The hotspots and trend analysis of clinical effect transformation of medical skill simulation training
Shun YAO ; Yabin TANG ; Chenyue YI ; Yao XIAO
Chinese Journal of Medical Education Research 2023;22(9):1308-1314
Objective:To explore the research hotspots and development trends of the transformation of virtual skill training to practical clinical ability in current medical simulation education, and to conduct visual bibliometric analysis.Methods:Taking 783 pieces of literature related to the transformation of simulation skill training to clinical competence collected from the Web of Science core collection database from 2006 to 2020 as data sources, CiteSpace V was used for visualization processing and analysis, so as to reveal the transformation effect and future research direction.Results:The number of published papers and citations increased exponentially with each year. The United States and Canada were the main research forces, the University of Toronto Medical Center contributed the largest number of research, and Professor McGaghie of Northwestern University was the author with the most published articles. According to the literature co-citation cluster analysis, it is found that the transformation of simulation skill training includes both operation and non-operation skills. High-frequency cited references reflect the knowledge base of this field and research to a certain extent. Research frontiers include the improvement of virtual reality simulators, clinical outcomes of simulated training in pediatrics, nursing, and emergency disciplines, and the design of randomized controlled clinical trials.Conclusion:The research on the clinical effect verification of simulation skill training is developing rapidly in the world. The research on medical skills' transformation represented by minimal invasive surgery such as endoscopy is a hot topic. Non-operational skills including communication skills, teamwork, pediatric emergency skills, and virtual reality technology simulation effects are the research frontiers. The number of researches on the effect of simulation training is small and the effect is unclear. In the future, more randomized controlled studies are still needed to determine the effectiveness of the transformation of simulation training to clinical competence.
5.Effect of preoperative blood pressure control on postoperative cardiovascularevents in patients with hy-pertension and gastrointestinal surgery
Chenyue GUO ; Yi LI ; Shengjin GE ; Changhong MIAO
The Journal of Clinical Anesthesiology 2017;33(9):856-859
Objective To study the effect of preoperative blood pressure control on postoperative cardiovascular events in patients with hypertension and gastrointestinal surgery. Methods A total of 238 hypertensive patients who underwent gastrointestinal surgery were selected and divided into control group (n =118)and non-control group (n =120)according to thehypotensor treatment.During the operation,the same anesthetic regimen was used.The use of vasoactive drugs was recorded during anesthesia.Bladder chalone C (Cys C)and cardiac troponin T (cTnT)were de-tected in blood before and after the operation,and so were N-terminal B type natriuretic peptide (NT-proBNP)level on the 1st and 5th day after the operation.The postoperative hospitalization time,fol-low-up of cardiovascular events 28 and 90 days after discharge were recorded.Results Compared with the non-control group,the total dosage of ephedrine in the control group was significantly re-duced [(3.41±1.04)mg vs (7.46 ± 3.29)mg,P <0.05 ],total dose of phenylephrinewas signifi-cantly reduced [(0.17±0.10)mg vs (0.46 ±0.16)mg,P <0.05],postoperative hospital stay was significantly shorter [(5.92±1.15)d vs (9.65±1.61)d,P <0.05],NT-proBNP level in the control group on the 1st day after the operation [(108.00 ± 47.11 )pg/L vs (250.38 ± 62.92 )pg/L,P <0.01]and 5 days after the operation [(62.07 ±25.31)pg/L vs (199.02 ± 60.32)pg/L,P <0.01 ] was obviously reduced.There was no statistical difference in Cys C andcTnT between the two group-safter operation.The incidence of cardiovascular adverse events in the control group was significantly lower than that in the non-control group (28 d:13.6% vs 62.7%,90 d:23.3% vs 23.3%,P <0.05).Conclusion Strict control of preoperative blood pressure control in patients with hypertension can significantly reduce the incidence of cardiovascular events.

Result Analysis
Print
Save
E-mail